Hepatitis C Virus-Induced FUT8 Causes 5-FU Drug Resistance in Human Hepatoma Huh7.5.1 Cells

Li, Shu; Liu, Xiao-Yu; Pan, Qiu; Wu, Jian; Liu, Zhi-Hao; Wang, Yong; Liu, Min; Zhang, Xiao-Lian

doi:10.3390/v11040378

Open AccessArticle

Hepatitis C Virus-Induced FUT8 Causes 5-FU Drug Resistance in Human Hepatoma Huh7.5.1 Cells

by

Shu Li

^†,

Xiao-Yu Liu

^†,

Qiu Pan

,

Jian Wu

,

Zhi-Hao Liu

,

Yong Wang

,

Min Liu

^* and

Xiao-Lian Zhang

^*

State Key Laboratory of Virology, Department of Immunology, Hubei Province Key Laboratory of Allergy and Immunology and Medical Research Institute, Wuhan University School of Basic Medical Sciences, Wuhan 430071, China

^*

Authors to whom correspondence should be addressed.

^†

These authors contributed equally to this work.

Viruses 2019, 11(4), 378; https://doi.org/10.3390/v11040378

Submission received: 26 February 2019 / Revised: 11 April 2019 / Accepted: 21 April 2019 / Published: 24 April 2019

(This article belongs to the Section Animal Viruses)

Download

Browse Figures

Versions Notes

Abstract

Hepatitis C virus (HCV) is a major cause of human chronic liver disease and hepatocellular carcinoma. Our recent studies showed that α1,6-fucosyltransferase (FUT8), a key glycosyltransferase, was the most up-regulated glycosyltransferase after the HCV infection of human hepatocellular carcinoma Huh7.5.1 cells. Here, we further studied the effects and possible mechanism of FUT8 on the proliferation of HCV and chemotherapy-resistance of HCV-infected Huh7.5.1 cells. The effects of FUT8 on the proliferation and drug resistance of HCV-infected Huh7.5.1 cells were analyzed by flow cytometry analysis (FCM), quantitative real-time polymerase chain reaction (qRT-PCR), Western blot analysis and lactate dehydrogenase (LDH) release assay. Results: We found that FUT8 not only promoted Huh7.5.1 proliferation by activating PI3K-AKT-NF-κB signaling, but also stimulated the expression of the drug-resistant proteins P-glycoprotein (P-gp) and multidrug resistance related protein 1 (MRP1) and enhanced the 5-fluorouracil (5-FU) chemo-resistance of Huh7.5.1 cells. Silencing of FUT8 reduced the cell proliferation and increased the 5-FU sensitivity of HCV-infected Huh7.5.1 cells. Inhibition of P-gp and MRP1 increased the 5-FU drug sensitivity in HCV infected Huh7.5.1 cells. HCV-induced FUT8 promotes proliferation and 5-FU resistance of Huh7.5.1 cells. FUT8 may serve as a therapeutic target to reverse chemotherapy resistance in HCV-infected Huh7.5.1 cells.

Keywords: hepatitis C virus (HCV); α-1,6 fucosyltransferase (FUT8); 5-fluorouracil (5-FU); drug-resistance

Share and Cite

MDPI and ACS Style

Li, S.; Liu, X.-Y.; Pan, Q.; Wu, J.; Liu, Z.-H.; Wang, Y.; Liu, M.; Zhang, X.-L. Hepatitis C Virus-Induced FUT8 Causes 5-FU Drug Resistance in Human Hepatoma Huh7.5.1 Cells. Viruses 2019, 11, 378. https://doi.org/10.3390/v11040378

AMA Style

Li S, Liu X-Y, Pan Q, Wu J, Liu Z-H, Wang Y, Liu M, Zhang X-L. Hepatitis C Virus-Induced FUT8 Causes 5-FU Drug Resistance in Human Hepatoma Huh7.5.1 Cells. Viruses. 2019; 11(4):378. https://doi.org/10.3390/v11040378

Chicago/Turabian Style

Li, Shu, Xiao-Yu Liu, Qiu Pan, Jian Wu, Zhi-Hao Liu, Yong Wang, Min Liu, and Xiao-Lian Zhang. 2019. "Hepatitis C Virus-Induced FUT8 Causes 5-FU Drug Resistance in Human Hepatoma Huh7.5.1 Cells" Viruses 11, no. 4: 378. https://doi.org/10.3390/v11040378

APA Style

Li, S., Liu, X.-Y., Pan, Q., Wu, J., Liu, Z.-H., Wang, Y., Liu, M., & Zhang, X.-L. (2019). Hepatitis C Virus-Induced FUT8 Causes 5-FU Drug Resistance in Human Hepatoma Huh7.5.1 Cells. Viruses, 11(4), 378. https://doi.org/10.3390/v11040378

Note that from the first issue of 2016, this journal uses article numbers instead of page numbers. See further details here.

Article Menu

Hepatitis C Virus-Induced FUT8 Causes 5-FU Drug Resistance in Human Hepatoma Huh7.5.1 Cells

Abstract

Share and Cite

Article Metrics

Article Access Statistics

Further Information

Guidelines

MDPI Initiatives

Follow MDPI